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XRCC1 interacts with the p58 subunit of DNA Pol alpha-primase and may coordinate DNA repair and replication during S

Nicolas Lévy1, Maren Oehlmann, François Delalande

  • 1FRE 3211, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, CNRS/Université de Strasbourg, Ecole Supérieure de Biotechnologie de Strasbourg, Boulevard S. Brant, BP 10413, F-67412, Illkirch Cedex, France.

Nucleic Acids Research
|March 24, 2009
PubMed

Insights

This study reveals how cells halt DNA synthesis during S phase when DNA damage occurs. It identifies a key protein interaction that connects DNA repair to replication, ensuring genomic stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Genomic stability relies on timely repair of DNA damage, especially single-stranded DNA breaks (SSBs) before replication.
  • The precise mechanisms by which cells manage DNA lesions during the S phase of the cell cycle remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms linking single-strand break repair (SSBR) to DNA replication during S phase.
  • To identify novel protein interactions involved in halting DNA synthesis in response to DNA damage.

Main Methods:

  • Proteomics to identify protein interactions.
  • In vitro and in vivo protein-protein interaction assays.
  • Biochemical assays using Xenopus egg extracts and HeLa cells.

Main Results:

  • The p58 subunit of DNA Pol alpha-primase was identified as a novel binding partner of XRCC1, a key SSBR protein.
  • Poly(ADP-ribose) binding to p58 inhibits primase activity by competing with DNA binding.
  • Overexpression of XRCC1-BRCT1 induced DNA damage responses, S phase delay, and interfered with replication fork assembly.

Conclusions:

  • XRCC1 plays a critical role in connecting the SSBR machinery to the replication fork.
  • This connection halts DNA synthesis upon DNA damage, thereby maintaining genomic stability.
  • The findings provide new insights into cell cycle regulation and DNA damage response pathways.

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